Electronically addressable chip-based molecular libraries (Lipshutz et al., Nature Genetics, 21:20, 1999; Pirrung, Chem. Rev. 97:473, 1997; Webb et al., J. Steroid Biochem. Mol. Biology, 85:183, 2003; Shih et al., J. Virological Methods, 111:55, 2003) have long been desired but have not been created. CombiMatrix Corporation scientists have been utilizing active-semiconductor electrode arrays that incorporate individually addressable microelectrodes to synthesize oligonucleotide and polypeptide molecules (U.S. Pat. No. 6,093,302; WO/0053625; Oleinikov et al., J. Proteome Res., 2:313, 2003; Sullivan et al., Anal. Chem., 71:369, 1999; Zhang et al., Anal. Chim. Acta, 421:175, 2000; and Hintsche et al., Electroanal. 12:660, 2000).
In this way, each unique set of molecules in a library can be located proximal to a selected electrode or set of electrodes that can, in turn, be used to monitor their behavior (Dill et al., Analytica Chimica Acta, 444:69, 2001). This is accomplished by coating the electrode-containing array devices with a porous polymer and then utilizing the electrodes to both attach monomers to the electrode array devices and then generate reagents capable of performing reactions on the monomers.
Pd(II) mediated oxidations are powerful synthetic tools that allow for the selective functionalization of organic molecules. Therefore, there is a need in the art for a combinatorial chemical synthesis device that could perform Pd(II) mediated oxidations on an electrode array. In particular, to perform a Pd(II) mediated oxidation on a selected electrode on the device. As a proof of principle, a Wacker oxidation (conversion of an alkene to a ketone) was used for this purpose. Such a device and process would expand the number of different molecules that could be constructed. Such a tool would allow for massively parallel electrochemical synthesis in small volumes on an electrode array device and create arrays containing highly diverse libraries of chemical compounds that are different from each other yet synthesized in parallel. Such “combinatorial libraries” could be synthesized rapidly, in small volumes and with high diversity.
Therefore, there is a need in the art to be able to perform rapid and diverse synthesis of chemical libraries on an electrode array device for large scale screening of combinatorial libraries. The present invention was made to address this need in the art.